Nicholson, AA;
Friston, KJ;
Zeidman, P;
Harricharan, S;
McKinnon, MC;
Densmore, M;
Neufeld, RWJ;
... Lanius, RA; + view all
(2017)
Dynamic Causal Modeling in PTSD and Its Dissociative Subtype: Bottom-Up Versus Top-Down Processing Within Fear and Emotion Regulation Circuitry.
Human Brain Mapping
, 38
(11)
pp. 5551-5561.
10.1002/hbm.23748.
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Abstract
Posttraumatic stress disorder (PTSD) is associated with decreased top–down emotion modulation from medial prefrontal cortex (mPFC) regions, a pathophysiology accompanied by hyperarousal and hyperactivation of the amygdala. By contrast, PTSD patients with the dissociative subtype (PTSD + DS) often exhibit increased mPFC top–down modulation and decreased amygdala activation associated with emotional detachment and hypoarousal. Crucially, PTSD and PTSD + DS display distinct functional connectivity within the PFC, amygdala complexes, and the periaqueductal gray (PAG), a region related to defensive responses/emotional coping. However, differences in directed connectivity between these regions have not been established in PTSD, PTSD + DS, or controls. Methods: To examine directed (effective) connectivity among these nodes, as well as group differences, we conducted resting-state stochastic dynamic causal modeling (sDCM) pairwise analyses of coupling between the ventromedial (vm)PFC, the bilateral basolateral and centromedial (CMA) amygdala complexes, and the PAG, in 155 participants (PTSD [n = 62]; PTSD + DS [n = 41]; age-matched healthy trauma-unexposed controls [n = 52]). Results: PTSD was characterized by a pattern of predominant bottom–up connectivity from the amygdala to the vmPFC and from the PAG to the vmPFC and amygdala. Conversely, PTSD + DS exhibited predominant top–down connectivity between all node pairs (from the vmPFC to the amygdala and PAG, and from the amygdala to the PAG). Interestingly, the PTSD + DS group displayed the strongest intrinsic inhibitory connections within the vmPFC. Conclusions: These results suggest the contrasting symptom profiles of PTSD and its dissociative subtype (hyper- vs. hypo-emotionality, respectively) may be driven by complementary changes in directed connectivity corresponding to bottom–up defensive fear processing versus enhanced top–down regulation.
| Type: | Article |
|---|---|
| Title: | Dynamic Causal Modeling in PTSD and Its Dissociative Subtype: Bottom-Up Versus Top-Down Processing Within Fear and Emotion Regulation Circuitry |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/hbm.23748 |
| Publisher version: | https://doi.org/10.1002/hbm.23748 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neuroimaging, Radiology, Nuclear Medicine & Medical Imaging, Neurosciences & Neurology, posttraumatic stress disorder, dynamic causal modeling, amygdala, prefrontal cortex, periaqueductal gray, fMRI, connectivity, POSTTRAUMATIC-STRESS-DISORDER, PERIAQUEDUCTAL GRAY, FUNCTIONAL CONNECTIVITY, LEARNED FEAR, LATENT CLASS, AMYGDALA, RESPONSES, NEUROSCIENCE, ANXIETY, THREAT |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10024298 |
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